Organic compounds and their preparation



United States Patent ORGANIC COMPOUNDS AND THEIR PREPARATION SydneyArcher, Delmar, N. Y., assignor to Sterling Drug Inc., New York, N. Y.,a corporation of Delaware No Drawing. Original application September 20,1954,

Serial No. 457,281. Divided and this application September 29, 1955,Serial No. 537,554

16 Claims. (Cl. 260-3095) This invention relates toisonicotinoylhydrazones of S-(oxoalkyl)-2-thiohydantoins and to theirpreparation, to the parent 5-(oxoalkyl)-2-thiohydanto-ins and to theirpreparation, and to the preparation of intermediate 2- amino-oxoalkanoicacids.

This application is a division of my copending application Serial No.457,281, filed September 20, 1954.

The S-(oxoalkyl)-2-thiohydantoin isonicotinoylhydrazones of my inventionhave the formula CONHN=C-XCHC=O I H-N l e-H I \E/ N where R is an alkylradical and X is an al'kylene radical, the total number of carbon atomsin R and X together being no greater than twelve. Thesecompounds, ineither the acid or salt form, are useful as chemotherapeutic agents, inparticular, for their antitubercular properties.

The alkyl radical designated above as R has from one to eleven carbonatoms and includes radicals such as methyl, ethyl, propyl, isopropyl,n-butyl, isoamyl, n-hexyl, n-octyl, n-decyl, n-undecyl, and the like.The alkylene radical designated above as X has from one to eleven carbonatoms and includes radicals such as and the like.

The 5- oxoalkyl -2-thiohydantoin isonicotinoylhydrazones of my inventionwere prepared by reacting isonicotinoylhydrazine with a 5- oXoal-kyl-2-thiohydantoin having the formula where R and X are defined asherein-above. This condensation reaction was carried out preferably byheating iso nicotinoylhydrazine with the appropriate 5- (oXoalkyl)-2-thiohydantoin in a polar solvent, preferably a lower alkanol such asmethanol, ethanol, isopropanol, etc. The temperature for carrying outthis condensation reaction is not critical and is limited only 'by theboiling point of the solvent used and by the decomposition temperatureof the reactants, i. e., several hundred degrees centigrade. In the sameWay the lower temperature limit is not criti cal, for example thereaction can be carried out in a polar solvent at room temperature,although the reaction then proceeds more slowly.

The 5-(oxoa1kyl)-2-thiohydantoin isonicotinoylhydrazones of my inventioncan be used in either thefree acid 2,763,662 Patented Sept. 18, 1956 iceMy invention also comprehends the above-described S-(oxoalkyl)-2thiohydantoins having the formula where R and X have the meanings givenhereinabove. Thesecompounds are useful as intermediates in thepreparation of my above described 5-(oXoalkyl)-2-thiohydantoinisonicotinoylhydrazones and, in addition, some of them, especially thosewhere X is CH2, in either the acid or salt form are useful aschemotherapeutic agents, in particular, vfor their antitubercularproperties.

I prepared these 5-(oxoalkyl)-2-thiohydantoins by heating aZ-amino-oxoalkanoic acid having the formula with a water-solubleinorganic thiocyanate and .a lower alkanoic acid anhydride, preferablyin the presence of a lower alkanoic acid, and thereafter deacylating thecorresponding l-a-cyl-S-(oxoalkyl)-2-thiohyantoin by heating it with astrong hydrolyzing agent, namely, a strong base or a strong mineral acidto remove the l-acyl group. The heating is normally done in the range ofabout 50 to 1:50 C. From the standpoint of convenience, accessibilityand. economy, acetic anhydride and acetic acid are preferred as thelower alkanoic acid anhydride and lower alkanoic acid, respectively;hydrochloric acid, as the strong mineral acid; sodium hydroxide, as thestrong base; and ammonium thiocyanate, as the water-soluble inorganicthiocyanate. The 5-(oxoalltyl)-2-thiohydantoins of my invention can beprepared in the absence of a lower alkanoic acid, e. g., acetic acid,although less desirably.

The 5-(oxoalkyl)-2-thiol1ydantoins of my invention can be used in eitherthe free acid form or in the form of their salts with relativelynon-toxic cations such as sodium, potassium, calcium, magnesium,ammonium, ethanolammonium, and the like. Therapeutic usefulness of thesethiohydantoins where X is CH2, i. e., the 2-oxoalkyl compounds, wasestablished by experiments in Swiss mice which were infectedintravenously with large inocula of virulent human-type tuberclebacilli. .The oral administration of my compounds resulted inprolongation of survival time, suppression of tuberculous lesions in thelungs, and inhibition of the multiplication of tubercle bacilli.

My invention further comprehends the process for the preparation of theintermediate 2-amino-oxoalk-anoic acids having the formula 0 R ii XCHOOOH where R and X have the meanings given hereinabove. I preparedthese intermediate amino-keto acids by heati Y Y 2,763,662

ing in an acidic medium a di-(lower alkyl)alpha-acylamido-alpha-(oxoalkyl)malonate having the formula where thetwo lower alkyl radicals each have from one to six carbon atomsinclusive and R is a lower alkyl radical having from one to five carbonatoms inclusive. The heating is normally done in the range of about 50to 150 C.

The intermediate di-(lower alkyl)alpha-acylamidoalpha-(oxoalkyl)malonates can be prepared by variousprocedures. One procedure that I found useful in preparing these esterswas the reaction of an oxoalkyl halide,

where halogen is preferably chlorine or bromine, with an alkali metalderivative, e. g., Na or Li, of a di-(lower alkyl)alpha-acylamidomalonate, obtainable for instance as described in U. S.Patent 2,521,809. The alkali metal derivative can be prepared byreaction of the substitutedmalonate with an alkali metal per se, or itsalkoxide, hydride, amide or organometallic derivative, e. g., alkalimetalaryl such as lithiumphenyl. The procedure is illustrated by thefollowing equation where the two lower alkyl radicals are ethyl:

o rt-ii-x ha1o en Met-C(O 0 0.1515);

NHO OR NHCOR where Met is an alkali metal cation. The oxoalkyl halides,or l-halo-alkanones,

O R-HlX-halogen can be prepared difi'erent ways. In preparing theseintermediates, I reacted a cadmium dialkyl, Cd(R)z (obtained from thecorresponding Grignard reagent), with the appropriate haloalkanoylhalide, halogen-X-CO-halogen, e. g., chloroacetyl chloride where X isCH2 and each halogen is chlorine. The haloalkanoyl halides can beprepared various ways well known in the art, e. g., by reaction ofthiouyl halide and the haloalkanoic acid available as given in Traite deChimie Organique, volume IX, pages 145 if, edited by Grignard et al.(Masson et Cie., Paris, 1939).

A useful method for the preparation of the intermedi ate di-(loweralkyl) alpha-acylamido-alpha-(3-oxoalkyl)- malonates, that is, where Xis CHzCHz, is the reaction of an alkyl vinyl ketone (or l-alken-B-one)with a di-(lower alkyl) alpha-acylamidomalonate, as illustrated by thefollowing equation where the two lower alkyl radicals are each ethyl:

NHCOR' My invention isfurther illustrated as follows without,

however, limiting it thereto.

EXAMPLE 1 A. Intermediate Z-amino-oxoalkanoic acids1-hal0-alkan0nes.-The preparation of these halo ketones is illustratedby the following preparation of 1- chloro-2-nonanone: The Grignardreagent was prepared from 48.8 g. of magnesium and 358 g. of n-heptylbromide in one liter of ether. The solution was chilled to 5 C., and anadditional liter of ether was added, followed by portionwise addition of196 g. of cadmium chloride. The mixture was allowed to warm slowly toabout 50-60 C. and then refluxed for one hour. About two liters ofbenzene was added and the condenser was set for downward distillation.The ether was then removed by distillation while benzene was added,keeping the volume constant throughout the distillation. When thetempera ture of the solution had reached 78 C., it was cooled to 10 C.and was treated with a solution of 226 g. of chloroacetyl chloride in400 ml. of benzene, this addition being made as rapidly as possible. Thetemperature rose rapidly to 25 C. and more slowly to 50 C. The reactionmixture was then stirred for two hours. It was poured into a mixture ofice and dilute sulfuric acid and the resulting layers were separated.The aqueous phase was washed with benzene and the benzene washings wereadded to the benzene layer. The resulting benzene solution was washedsuccessively with water, saturated sodium bicarbonate solution, waterand finally with saturated T sodium chloride solution.

The benzene solution was dried over anhydrous calcium sulfate anddistilled in vacuo to yield a residue which was then distilled underreduced pressure. This distillation yielded 140.8 g. of 1-chloro-2-nonanone, B. P. 67-71 C. at 0.3 mm.; 11

Analysis.-Calcd. for CsHuClO: Cl, 20.01. Found: Cl, 19.90.

Other l-chloro-Z-alkanones prepared following the aboveprocedure aregiven in Table I.

TABLE I ll RCOH1C1 R Yield, 13. P., 0.

Percent n-CaHn 33 7879 at 0.2 mm.

nOflHlIi 47. 5 6762 at 0.1 mm. n-CsHu 43. 5 5057 at 1.5 mm. I1 Cal-In27.5 85 at 1 mm. n-C4H 40 M.P. 3839 Other l-halo-alkanones that can beprepared according to the foregoing procedure using the appropriatereaccompounds is illustrated by the following preparation of2-amino-4-oxoundecanoic acid: Phenyllithium was prepared from 14.7 g. oflithium wire (suspended in 250 ml. of ether) and 157 g. of brornobenzenein 500 ml. of ether. The solution was filtered and 217 g. of diethyl.alpha-acetamidomalonate in ml. of benzene was added. The ether wasremoved by distillation. A solution of 140.8 g. of 1-chloro-2-nonanonein 200 ml. of henzene was added and the mixture was refluxed for sixteenhours. The lithium halides formed in the reactions were filtered off andthe solvent removed by distilling in vacuo. The residue was refluxed forsixteen hours with 1500 ml. of 6 N hydrochloric acid. The mixture waschilled and the 2-amino-4-oxoundecanoic acid hydrochloride thatseparated was collected on a filter and washed thoroughly with ether.This amino acid hydrochloride was dissolved in ethanol, the solutionmade faintly alkaline with am- Found TABLE II t r R-l-CH2CH C O O H RYield, M.I., O.

Percent 11-0 111; 24 182-183 n-C Hm B 12 174-176 n-CsHu 11 176-178n-CnHin 20 165-167 n-O Hn B 8. 166.1-168 Sodium derivative of diethylalpha-acetamid omalonate used; it was prepared by reacting sodiumethoxide with diethyl alphaacetamidomalonate in ethanol solution.

Other 2-amino-oxoalkanoic acids that can be prepared according to theabove procedure include 2-amino-4- oxopentanoic acid,2-amino-4-oxoheptanoic acid, Z-amino- -methyl-4-ox0undecan0ic acid,2-amino 9-methy1-4- oxodecanoic acid, 2-a1nino 4 oxotetradecanoic acid,2-amino-6-oxooctanoic acid, 2 amino 14 oxopentadecanoic acid,2-arnino-10-oxoundecanoic acid, Z-amino- 8-oxoundecanoic acid, and thelike.

In the preparation of my intermediate 2-amino-4-oxoalkanoic acids theforegoing procedure can be modified by using potassium in place oflithium or sodium, and by using other lower alkyl esters of otheralpha-(lower carboxylic acylamido)-malonic acids in place of diethylalpha-acetamidomalonate.

B. 5-(oxoalkyl)-2-thiohydantoins The preparation of these compounds isillustrated as follows for the preparation of5(2-oxononyl)-2-thiohydantoin: A mixture of 21.5 g. of2-amino-4-oxoundecanoic acid, 13.35 g. of ammonium thiocyanate, 60 ml.of acetic anhydride and 6.7 ml. of acetic acid was refluxed withstirring for twenty minutes, and then poured into ice water. The solidN-acetyl derivative that separated was collected and boiled for fortyminutes with a mixture containing 44.5 ml. each of water, ethanol andconcentrated hydrochloric acid. The mixture was chilled and the productcollected. Two crystallizations of this product from ethanol yieldedabout 16.5 g. of S-(Z-oxononyD-Z- thiohydantoin, M. P. 104.0108.9 C.(corn).

Analysis.-Calcd. for C12H20N2O2S: N, 10.93; S, 12.51. Found: N, 10.94;S, 12.61.

Other 5-(2-oxoalkyl)-2-thiohydantoins prepared according to theforegoing procedure are given in Table III.

Analysis M. P., O. R (corn) Galcd. Found N S N S n-OsHn 110. 7-112. 710. 36 11. 86 10. 35 12.05 n-CoHm 110. 3-113. 0 9. 85 11.27 9. 72 11. 12Il-CoHrs 98 3-1000 11. 53 13.22 11. 53 13. 48 n-CrHn 98. 2-101. 2 12. 2714. 04 12.15 13. 77 11O4Hr 88. 7-101. 3 13. 08 13.11

Other 5-(oxoalkyl)-2-thiohydantoins that can be prepared according tothe above procedure include 5-(2-0xopropyl)-2-thiohydantoin, 5 (2oxopentyl) 2 thiohydantoin, 5-(8-methyl-2-oxononyl)-2-thiohydantoin,5-(7- methyl-Z-oxooctyl) -2-thiohydantoin, 5- 2-oxododecyl) -2-thiohydantoin, 5-(4-oxohexyl) -2-thiohydantoin, 5-(12-oxotridecyl)-2-thiohydantoin, 5 (8 oxononyl)-2-thiohydantoin,5-(6-oxononyl)-2-thiohydantoin, and the like.

EXAMPLE 2 A. Intermediate Z-amz'no-S-oxoalkanoic acids Theseintermediates were prepared according to the procedure as outlined inthe specification hereinabove and as illustrated by the following seriesof equations:

RGOCH=CH2 OHaCONHCH(OOOCrH5)r RC0CH:2CH2G(COOOzH5)2 NHOOCHs r! RC 0GH2CH2CH(NHQ) C O OH where R is defined as given hereinabove. Thisprocedure is further illustrated by the following examples.

1-clzloro-3-alkmz0nes.-The preparation of these chloro ketones isillustrated by the following preparation of 1-chloro-3-octanone: A threeliter three-necked flask was charged with 695 g. of chloroform and 199g. of aluminum chloride. This mixture was cooled to 10 C. and saturatedwith ethylene. To this mixture was added 200 g. of caproyl chloride(n-hexanoyl chloride) in one portion and stirring at 10 C. was continuedfor two hours as ethylene was bubbled continuously through the mixture,which was then allowed to stand overnight. The reaction mixture waspoured into ice water which had been acidified with hydrochloric acid.The aqueous layer was extracted with chloroform, and the chloroformextract was Washed with water and concentrated. The residual materialwas distilled in vacuo yielding 72 g. of 1-chloro-3-octanone, B. P. 7278C. at 4.8 mm.

Other 1-chloro-3-alkanones that were prepared according to the foregoingprocedure include 1-chloro-3- heptanone, B. P. 7279 C. at 10 mm. and1-chloro-3- hexanone, B. P. 57-63 C. at 9 mm.

Other l-chloro-3-alkanones that can be prepared following the aboveprocedure include 1-chloro-3-butanone, 1-chloro-3-pentanone,1-c11loro-3-nonanone, l-chloro-3- tridecanone and1-chloro-6-methyl-3-heptanone.

Alkyl vinyl ketortes (I-alken-3-0nes).-Preparati0n of these unsaturatedketones is illustrated by the following preparation of n-arnyl vinylketone (1-octen-3-one): A mixture of 72 g. of 1chloro-3-octanone, 70.6g. of sodium benzoate and 300 ml. of Dowtherm A (mixture of diphenylether and biphenyl) was charged into a flask equipped with an etficientstirrer and a condenser set for downward distillation. The distillatewas collected until the temperatures of the vapors reached 210 C. It wasthen dried over anhydrous calcium sulfate and distilled, yielding 22 g.of n-amyl vinyl ketone, B. P. 5762 C. at 13 mm.

Other vinyl ketones prepared according to the foregoing procedure aren-propyl vinyl ketone, B. P. 64 C. at 70 mm. and n-butyl vinyl ketone,B. P. 38-43 C. at 9 mm.

Other alkyl vinyl ketones that can be prepared according to the aboveprocedure include methyl vinyl ketone, ethyl vinyl ketone, n-hexyl vinylketone, n-decyl vinyl ketone and isobutyl vinyl ketone.

Lower alkyl alpha-(3-0x0alkyl)-alplm-acelamidomalo nates.-Thepreparation of these compounds is illustrated by the followingpreparation of diethyl alpha-acetamidoalpha-(3-oxooctyl)-rnalonate: To amixture containing 54.6 g. of diethyl alpha-acetamidomalonate, 203 m1.of ethanol and 1.27 ml. of triethylamine cooled in ice was addeddropwise over thirty minutes 32 g. of n-amyl vinyl 7 ketone. The mixturewas then allowed to stand at room temperature for about sixteen hours,after which time it was filtered and distilled in vacuo to remove thesolvent. The crystalline residue was triturated with petroleum ether andfiltered; yielding 55 g. of diethylalpha-acetamidoalpha-(3-oxooctyl)malonate. A sample was recrystallizedfrom petroleum ether for analysis, M. P. 60-61" C.

Analysis.--Calcd. for C17H29NO6: N, 4.08. Found: N, 4.40.

Other diethyl alpha-acetamido-alpha-(3-oxoalkyl)malonates preparedaccording to the foregoing procedure are diethyl alpha acetamidoalpha-(3-oxoheptyl)malonate (from n-butyl vinyl ketone) M. P. 62-64 C.when recrystallized from petroleum ether; and diethylalphaacetamido-alpha-(3-oxohexyl)malonate (from n-propyl vinyl ketone)M. P. 83-845 C. when recrystallized from aqueous methanol.

Other dialkyl alpha-acetamido-alpha-(3-oxoalkyl)malonates that can beprepared according to the above pro cedure include di-n-butylalpha-acetamido-alpha-(3-oxobutyl)malonate, di-n-propylalpha-acetamido-alpha-(3- oxopentyl)malonate, diethylalpha-acetamido-alpha-(3- oxononyl)malonate, diethylalpha-acetamido-alpha-(3- oxotridecyl)malonate and diethylalpha-acetamido-alpha- (6-methyl-3-oxoheptyl)rnalonate.

2-amin0-5-0xoalkanoic acids.These intermediate acids were prepared fromthe corresponding dialkyl alpha-acetamido-alpha-(3-oxoalkyl)malonatesaccording to the procedure as illustrated as follows for the preparationof 2-amino-5-oxodecanoic acid: A mixture of 27.5 g. of diethylalpha-acetamido-alpha-(3-oxooctyl)malonate and 200 ml. .of concentratedhydrochloric acid was refluxed for six hours and then concentrated todryness by distilling in vacuo on a steam bath. The residue wasdissolved in a. small amount of water and the solution filtered. Thefiltrate was made slightly basic and was chilled. The precipitate waswashed with water and acetone and then air dried, yielding 8.5 g. ofZ-amino-S-oxodecanoic acid.

Other Z-amino-S-oxoalkanoic acids prepared according to the foregoingprocedure are Z-amino-S-oxononanoic acid, M. P. 125-128" C. and2-amino-5-oxooctanoic acid, M. P. 105106 C.

Other Z-amino-S-oxoalkanoic acids that can be prepared according to theabove procedure include Z-amino- S-oxohexanoic acid,2-amino-5-oxoheptanoic acid, 2- amino-S-oxoundecanoic acid,2-amino-5-oxopentadecanoic acid and 2-amino-8-methyl-5-oxononanoic acid.

In the preparation of the foregoing 2-amino-5-oxoalkanoic acids, otherlower alkyl esters of alpha-(lower carboxylic acylamido)malonic acidscan be used in place of diethyl alpha-acetamidomalonate.

B. 5 (3-0x0alkyl -2-thiohydant0ins These compounds were preparedfollowing the procedure described above in Example 1B. Illustrative ofthese compounds are those given in Table IV.

TABLE IV Other 5-(3-0xoalkyl)-2-thiohydantoins that can be preparedaccording to the above procedure include 5-(3- oxobutyl-2-thiohydantoin, 5 3-oxopentyl) -2-thiohydantoin,5-(3-ox0nonyl)-2-thiohydantoin, 5-(3-oxotridecyl)- Z-thiohydantoin and 56-methyl-3-oxoheptyl) -2-thiohydantoin.

EXAMPLE 3 5-(0xoalkyl)-2-thi0hya'ant0in isonicotinoylhydrazones Thepreparation of these compounds is illustrated by the followingpreparation of 5-(2-oxononyl)-2-thiohydantoin isonicotinoylhydrazone: Amixture containing 12 g. of 5-(2-oxononyl)-2-thiohydantoin, 5.48 g. ofisonicotinoylhydrazine and 200 ml. of methanol was refluxed for fivehours. The methanol was removed by distillation in vacuo and the residuewas triturated with n-hexane to yield a solid material. The solid wascollected, washed with n-hexane and recrystallized twice, withcharcoaling, from isopropanol, thereby yielding the product,5-(2-oxonony1)-2thiohydantoin isonicotinoylhydrazone, M. P. 168.5-l74.9C. (corr.).

Analysis.Calcd. for C1sH25N5O2S: N, 18.65; S, 8.54. Found: N, 18.61; S,8.85.

The above reaction also can be carried out at lower temperatures, i. e.,room temperature, however the reaction time is increased, and standingfor a day to several days may be desirable to ensure complete reaction.

Other 5-( oxoalkyl)-2-thiohydantoin isonicotinoylhydrazones preparedaccording to the foregoing procedure are given in Table V.

zones that can be prepared according to the above procedure include5-(2-oxoundecyl)-2-thiohydantoin isonicotinoylhydrazone, 5 (2oxopropyl)-2-thiohydantoin iso nicotinoylhydrazone, 5 (2oxopentyl)-2-thiohydantoin isonicotinoylhydrazone, 5(8-methyl-2-oxonoyl)-2-thiohydantoin isonicotinoylhydrazone,5-(7-methyl-2-oxooctyl)-2-thiohydantoin isonicotinoylhydrazone,5-(2-oxododecyl)-2-thiohydantoin isonicotinoylhydrazone, 5-(4-oxohexyl)-2-thiohydantoin isonicotinoylhydrazone, 5-(12-oxotridecyl)-2-thiohydantoin isonicotinoylhydrazone, 5-(S-oxononyl)-2-thiohydantoin isonicotinoylhydrazone, 5-(6-oxononyl)-2-thiohydantoin isonicotinoylhydrazone, 5-(S-oxohexyl)-2-thiohydantoin isonicotinoylhydrazone, 5-

(3-oxobu-tyl)-2 th'iohydantoin isonicotinoylhydrazone, 5-'(3-oxopentyl)-2-tl1iohydantoin isonicotinoylhydrazone, 5-

(3oxononyl-2t*hiohydantoin isonicotinoylhydrazone, 5- (3oxotridecyl)-2-thiohydantoin isonicotinoylhydrazone and5-(6-methyl-3-oxoheptyl)-2-thiohydantoin isonicotinoylhydragone.

9 I claim: 1. A 5'(oxoalkyD-Z-thiohydantoin having the formulaR("J-XCH-G=O H-N N-H where R is an alkyl radical and X is an alkyleneradical, the total number of carbon atoms in R and X together being nogreater than twelve.

2. A 5-(2-oxoalkyl)-2-thiohydantoin having the formula where R is analkyl radical having one to eleven carbon atoms inclusive.

3. A -(3-oxoalkyl)-2-thiohydantoin having the formula where R is analkyl radical having one to ten carbon atoms inclusive.

. 5- 2-oxoheptyl) -2-thiohydantoin. 5-(2-0xooctyl)-2-thiohydantoin.

5-( 2-oxononyl -2-thiohydantoin. 5-(2-oxodecyl)-2-thiohydantoin. 5-3-oxoootyl) -2 thiohydanttoin. The process of preparing a5-(oxoalkyl)-2-thiohydantoin having the formula where R is an alkylradical and X is an alkylene radical, the total number of carbon atomsin R and X together being no greater than twelve, which comprisesheating an amino-keto acid having the formula with a water-solubleinorganic thiocyanate and a lower alkanoic acid anhydride, andthereafter deacylating the correspondingl-acyl-S-(oxoalkyl)-2-thiohydantom.

10 10. The process of preparing a 5-(2-oXoalkyl)-2-thiohydantoin havingthe formula where R is an alkyl radical having one to eleven carbonatoms inclusive, which comprises heating a 2-amino-4- oxoalkanoic acidhaving the formula with a water-soluble inorganic thiocyanate and alower alkanoic acid anhydride, and thereafter deacylating the resulting1-acyl5-(2-oxoalkyl)-2-thiohydantoin.

11. The process of preparing a 5-(3-oxoalkyl)-2-thiothydantoin havingthe formula II RCOHzCHr-CH-C=O H-N N-H c I! s where R is an alkylradical having one to ten carbon atoms inclusive, which comprisesheating a 2-arnino-5- oxoalkanoic acid having the formula with awater-soluble inorganic thiocyanate and a lower alkanoic acid anhydride,and thereafter deacylating the resulting 1-acy1-5 3-oxoalkyl)-2-thiohydantoin.

12. The process of preparing 5-(2-oxoheptyl)-2-thiohydantoin whichcomprises heating 2-amino-4-oxononanoic acid with a water-solubleinorganic thiocyanate and acetic anhydride, and thereafter deacetylatingthe resulting l-acetyl-S-(2-oxoheptyl)-2-thiohydantoin.

13. The process of preparing 5-(2-oxooctyl)-2-thiohydantoin whichcomprises heating 2 amino-4-oxodecanoic acid with a water-solubleinorganic thiocyanate and acetic anhydride, and thereafter deacetylatingthe resulting l-acetyl-S-(2-oxoocty1)-2-thiohydantoin.

14. The process of preparing 5-(2-oxononyl)-2-thiohydantoin whichcomprises heating 2-amino-4-oxoundecanoic acid with a water-solubleinorganic thiocyanate and acetic anhydride, and thereafter deacetylatingthe resulting l-acetyl-S-(2-oxononyl)-2-thiohydantoin.

15. The process of preparing 5-(2-oxodecyl)-2-thiohydantoin whichcomprises heating 2-amino-4-ketododecanoic acid with a water-solubleinorganic thiocyanate and acetic anhydride, and thereafter deacetylatingthe resulting l-acetyl-S-(2-oxodecyl)-2-thioh.ydantoin.

16. The process of preparing 5-(3-oxooctyl)-2-thiohydantoin whichcomprises heating Z-amino-S-oxodecanoic acid with a water-solubleinorganic thiocyanate and acetic anhydride, and thereafter deacetylatingthe resulting l-acetyl-S-(3-oxooctyl)-2-thiohydantoin.

No references cited.

1. A 5-(OXOALKYL)-2-THIOHYDANTOIN HAVING THE FORMULA